Coming off a career-best 40 points in a win against Dallas on Wednesday, DeRozan helped the Raptors open as much as a 13-point lead down the stretch after they held only a two-point advantage heading into the fourth quarter.
DeRozan made 13-of-16 from the foul line, five of the free throws coming in the final 25 seconds.
Lowry scored 18 points, claimed 10 rebounds and dealt out 13 assists for the fourth triple-double of his career. He made 7-of-11 from the field.
Toronto won its second straight to move two games above the .500 mark. The Raptors are one of five teams in the Eastern Conference with a winning record.
Michael Carter-Williams led Philadelphia with 20 points while Thaddeus Young had 16.